Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders
Abstract
:1. Introduction
2. Results
2.1. Family 1
2.2. Family 2
3. Discussion
4. Materials and Methods
4.1. Routine Coagulation Assays
4.2. Fibrinolytic System Assays
4.3. Global Hemostasis Testing
4.4. DNA Preparation and Genetic Analysis
4.5. Protein Modelling
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Types of Congenital Fibrinogen Disorders | Bleeding Features | Thrombotic Features | Asymptomatic |
---|---|---|---|
afibrinogenemia | 1 | - | - |
hypofibrinogenemia | 2 | 5 | 6 |
hypodysfibrinogenemia | - | - | 1 |
dysfibrinogenemia | 10 | 1 | 28 |
Family Members | Clotting Time (s) | Fibrinogen (g/L) | |||||
---|---|---|---|---|---|---|---|
PT | APTT | TT | RT | Clauss | LIA | ||
A. Family 1 | |||||||
Proband (28) | II–3 | >300 | >300 | >300 | >150 | UD | 0.0 |
Son (1) | III–1 | 11.7 | 23.6 | 19.5 | 20.1 | 1.1 | 1.2 |
Elder sister (34) | II–2 | 11.7 | 35.6 | 17.6 | 19.9 | 1.6 | 1.4 |
The eldest sister (38) | II–1 | 11.5 | 31.1 | 18.3 | 18.6 | 1.7 | 1.5 |
Father (64) | I–1 | 11.8 | 28.0 | 16.0 | 18.1 | 1.3 | 1.3 |
Mother (62) | I–2 | 11.1 | 23.8 | 13.9 | 19.7 | 1.5 | 1.5 |
Normal range | - | 10.4–12.6 | 22–32 | 15–22 | 16–22 | 1.8–4.2 | 1.8–4.2 |
B. Family 2 | |||||||
Proband (62) | I–1 | 14.2 | >300 | 16.4 | 26.4 | 0.5 | 0.5 |
Daughter (23) | II–1 | 14.2 | 26.3 | 10.6 | 15.8 | 1.2 | 1.1 |
Elder son (34) | II–2 | 12.7 | 23.8 | 12.4 | 17.4 | 1.0 | 1.3 |
The eldest son (37) | II–3 | 12.5 | 24.8 | 12.9 | 17.9 | 1.4 | 1.7 |
Normal range | - | 10.4–12.6 | 22–32 | 15–22 | 16–22 | 1.8–4.2 | 1.8–4.2 |
Exon | cDNA | Status | Type | Bleeding | Thrombosis | Reference |
---|---|---|---|---|---|---|
2 | 3282C>T (17)Arg>stop | homozyg | afib | yes | no | [26] |
3 | c.352C>T (88)Glu>stop | compound heterozyg | afib | yes | no | [22] |
6 | c.887G>A (266)Trp>stop | homozyg | afib | yes | - | [27] |
7 | c.1105C>T (339)Gln>stop | heterozyg | hypofib | yes | no | [28] |
8 | nt.7893C>T (393)Gln>stop | heterozyg | hypofib | yes | no | [29] |
Exon | cDNA | Status | Type | Bleeding | Thrombosis | Reference |
---|---|---|---|---|---|---|
5 | 5909A>G (236)Tyr>Cys | compound heterozyg | hypofib | yes | yes | [33] |
6 | c.285T>C (269)Tyr>His | homozyg | afib | yes | yes | [22] |
6 | c.919G>T (277)Ala>Ser | homozyg | afib | no | yes | [34] |
8 | c.G1391A (434)Gly>Asp | homozyg | afib | yes | yes | [35] |
8 | c.1415G>T (442)Gly>Val | homozyg | hypofib | no | yes | [22] |
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Simurda, T.; Zolkova, J.; Snahnicanova, Z.; Loderer, D.; Skornova, I.; Sokol, J.; Hudecek, J.; Stasko, J.; Lasabova, Z.; Kubisz, P. Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders. Int. J. Mol. Sci. 2018, 19, 100. https://doi.org/10.3390/ijms19010100
Simurda T, Zolkova J, Snahnicanova Z, Loderer D, Skornova I, Sokol J, Hudecek J, Stasko J, Lasabova Z, Kubisz P. Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders. International Journal of Molecular Sciences. 2018; 19(1):100. https://doi.org/10.3390/ijms19010100
Chicago/Turabian StyleSimurda, Tomas, Jana Zolkova, Zuzana Snahnicanova, Dusan Loderer, Ingrid Skornova, Juraj Sokol, Jan Hudecek, Jan Stasko, Zora Lasabova, and Peter Kubisz. 2018. "Identification of Two Novel Fibrinogen Bβ Chain Mutations in Two Slovak Families with Quantitative Fibrinogen Disorders" International Journal of Molecular Sciences 19, no. 1: 100. https://doi.org/10.3390/ijms19010100